1-oxygenated 1, 2, 3, 3alpha, 3beta, 4, 5, 9, 11, 11alpha, 11beta, 12, 13, 13alpha-tetradecahydro-11alpha, 13alpha-dimethylcyclopenta [7, 8] phenanthro [2, 3-c] [1, 2, 6] thiadiazine 8, 8-dioxides and congeners



l-OXYGENATED 1,2,3,3a,3b,4,5,9,11,11a,11b,12,13,l3a- TETRADECAHYDRO 11a,13a DIMETHYLCY- CLOPENTAU,8]PHENANTHRO[2,3 c][1,2,6]THIA- 5 DIAZKNE 8,8-DIOXIDES AND CONGENERS James R. Deason, Skolrie, Iil., assignor to G. D. Searle & Co., Chicago, Ill., a corporation of Delaware No Drawing. Filed Mar. 2, 1966, Ser. No. 531,080 6 Claims. ((31. 260-2395) This invention relates to l-oxygenated 1,2,3,3a,3b,4,5, 9,11,1la,l 1b,12,13,13a-tetradecahydro l1a,l3a dimethylcyclopenta[7,8]phenanthro[2,3-c] [1,2,6]thiadiazine 8, 8-dioxides and congeners, and to processes for the preparation thereof. More particularly, this invention provides new, useful, and unobvious chemical compounds of the formula wherein the dotted lines represent optional double bonds, R represents hydrogen or a lower alkyl radical, and Z represents a carbonyl radical or a radical of the formula in which R represents hydrogen or a lower alkanoyl radical and R" represents hydrogen or a lower alkyl radical. 3

Those skilled in the art will recognize that lower alkanoyl radicals are radicals of the formula -CO-lower alkyl and lower alkyl radicals are monovalent, saturated, acyclic straightor branched-chain, hydrocarbon groupings of empirical formula (R, R", and the dotted lines retaining the meanings pre viously assigned) with sulfamide in methanol saturated with hydrogen chloride and esterifying the resultant polyhydro l hydroxycyclopenta[7,8]phenanthro[2,3-c][1,

Patented Dec. 12, 1967 2,6]thiadiazine 8,8-dioxide if and as desired by heating with a lower alkanoic acid anhydride or chloride lower alkyl-CO I lower alkylC 0 01 lower alkylC O in the presence of pyridine or, optionally, oxidizing the enformulated l-hydroxy products wherein R" represents hydrogen by contacting with chromic anhydride and sulfuric acid in an acetonic medium to produce the l-oxo compounds of the invention.

The following examples describe in detail compounds illustrative of the present invention and methods which have been devised for their preparation. However, the invention is not to be construed as limited thereby, eith r in spirit or in scope, since it will be apparent to those skilled in the art of organic synthesis that many modifications, both of materials and of methods, may be practiced without departing from the purpose and intent of this disclosure. Throughout the examples hereinafter set forth, temperatures are given in degrees Centigrade and relative amounts of materials in parts by weight, except as otherwise noted. Specific rotations are referred to the D line of sodium. 0

EXAMPLE 1 1,2,3,3a,3b,4,5,9,I1,]1a,]]b,l2,13,13a tetradecahydro-I- hydl'oxy 1 Ia,ISa-dimerhylcyclopenta[7,8] phena-nthro [2,3-0] [1,2,6] thiadiazine 8,8-di0xide Hydrogen chloride is passed through a solution of 33 parts of 17fl-hydroxy-2-hydroxymethyleneandrost-4-en-3- one and 10 parts of sulfamide in 790 parts of methanol for 30 minutes, whereupon the flow of gas is stopped and the resultant mixture heated at the boiling point under reflux for 30 minutes, then allowed to stand at room temperatures overnight. A yellowish-green solid precipitates. Solvent is removed by vacuum distillation. The residue is triturated and washed with acetone, then dried in air to give 1,2,3,3a,3b,4,5,9,l1,11a,1 1b,12,13,13a tetradecahydro-l hydroxy 11a,13a dimethylcyclopenta[7,8]phenanthro[2,3-c] [1,2,6]thiadiazine 8,8-dioxide melting at approximately 299-300. The specific rotation of a 1.025% solution in' pyridine at 26 is 176. The product has the formula EXAMPLE 2 I acetoxy 1,2,3,3a,3b,4,5,9,11,1]a,IIb,I2,I3,]3a-tetradecahydro 11a,13a dimezhylcyclopema[7,8]phenavlthr0[2,3-c] [1,2,6]thz'adiazine 8,8-di0xide A solution of 5 parts of 1,2,3,3a,3b,4,5,9,1l,11a,11b, 12,13,13a-tetradecahydro-l-hydroxy 11a,13a dimethylcyclopenta[7,8] phenanthro [2,3-c] [1,2,6]thiadiazine 8,8- dioxide in 25 parts of acetic anhydride and25 parts of pyridine is heated at around for 1 hour, then poured into 5 volumes of ice water. Insoluble solids are filtered off and crystallized from a mixture of acetone and methanol, using decolorizing charcoal in process. Recrystallization from methanol alone, again using decolorizing charcoal, affords l-acetoxy-l,2,3,3a,3b,4,5,9,11,11a,l1b, 12,13,13a-tetradecahydro 1la,l3a dimethylcyclopenta [7,8]phenanthro[2,3-c] [1,2,6]thiadiaziue 8,8-dioxide as a yellow monomethanol solvate melting at 282-284. Specific rotation of a 1.002% solution of the methanolate in 3 chloroform at 23* is 168.5. Solvent of crystallization is removed by prolonged heating in vacuo. The non-s01- vated product has the formula H3O OCOCH:

EXAMPLE 3 1,2,3,3a,3b,4,5,9,11,110,11 b,1 2,13,] 3a tetradecahydro- J1a,13a dimethyl 1-0x0cycl0penta[7,8] phenanthro- [2,3-c] [1,2,6] thiadiazine 8,8-di0xide To 50 parts of 1,2,3,3a,3b,4,5,9,11,11a,llb,l2,13,13atetradecahydro 1 hydroxy-l1a,13a-dimethylcyclopenta [7,8]phenanthro[2,3 c][1,2,6]thiadiazine 8,8 dioxide suspended in 790 parts of acetone is added a solution prepared by dissolving 14 parts of chromic anhydride in 21 parts of concentrated sulfuric acid and 28 parts of water. The resultant mixture is stirred minutes and then poured into 2500 parts of water. The resultant clear solution is diluted with just sufficient additional water to induce cloudiness, then refrigerated. The insoluble solid which precipitates is filtered off and dried in air. The product thus isolated is 1,2,3,3a,3b,4,5,9,11,11a,11b,12,13,13a-tetradecahydro l1a,13a dimethyl-l-oxocyclopenta[7,8]- phenanthro[2,3 c] [1,2,6]thiadiazine 8,8-dioxide melting at approximately 301. It has the formula H36 fl) H3O HN Ga s EXAMPLE4 1,2,3,3a,3b,4,5,5a,6,9,11,11a,11b,12,13,13a hexadecahydro 1 hydroxy 1,110,]3a-trimethylcycl0penta[7,8] phenanthr0[2,3 c] [1,2,6]thiadiazine 8,8-di0xide HsC OH EXAMPLE 5 1 ethyl 1,2,3,3a,3b,9,11,I1a,11b,12,13,13a dodecahydro 1-hydr0xy-11w,13a,dimethylcycl0penta[7,8]phenanthro [2,3-0] [1,2,6] thiadiazine 8,8-di0xide Substitution of 35 parts of 17a-ethyl-17B-hydroxy-2- hydroxymethyleneandrosta 4.6-dien-3-one for the 175- hydroxy-Z-hydroxymethyleneandrost-4-en-3-one called for ,4 in Example 1 affords, by the procedure there detailed, 1- ethyl 1,2,3,3a,3'b,9,1l,11a,11b,12,13,13a dodecahydro- 1 hydroxy 11a,13a-dimethylcyclopenta[7,8]phenanthro[2,3-c][1,2,6]thiadiazine 8,8-dioxide, the formula of which is H30 OH What is claimed is: 1. A compound of the formula wherein the dotted line in ring A represents an optional double bond, the dotted line in ring B represents an op tional double bond when there is a double bond in ring A, and Z represents a member of the class consisting of the carbonyl radical and a radical of the formula wherein R represents a member of the class consisting of hydrogen and a radical of the formula CO-lower alkyl and R" represents a member of the class consisting of hydrogen and an alkyl of the formula n 2n+1 wherein n represents a positive integer less than 4.

2. A compound according to claim 1 which is 1,2,3, 3a,3b,4,5,9,l1,11a,11b,12,13,13a tetradecahydro 1 hydroxy 1la,13a dimethylcyclopenta[7,8]phenanthro[2, 3-c] [1,2,6]thiadiazine 8,8-di0xide.

3. A compound according to claim 1 which is l-acetoxyl 1,2,3,3a,3b,4,5,9,11,1la,11b,12,13,13a tetradecahydro l1a,13a dimethylcycl0penta[7,8]phenanthro[2, 3-c] [1,2,6]thiadiazine 8,8-dioxide.

4. A compound according to claim 1 which is 1,2,3, 3a,3b,4,5,9,1l,11a,11b,l2,13,13a tetradecahydro 11a, 13a dimethyl 1 oxocyclopenta[7,8]phenanthIo[2,3-c] [1,2,6] thiadiazine 8,8-dioxide.

5. A compound according to claim 1 which is 1,2,3, 3a,3b,4,5,5a,6,9,1l,11a,11b,12,13,13a hexadecahydro-lhydroxy 1,11a,13a trimethylcyclopenta[7,8]phenanthro [2,3c-1 [1,2,6]thiadiazine 8,8-dioxide.

6. A compound according to claim 1 which is l-ethyl- 1,2,3,3a,3b,-9,11,1la,11b,12,13,13a dodecahydro 1 hydroxy l1a,13a dimethylcyclopenta[7,8]phenanthro[2, 3-c] [1,2,6]thiadiazine 8,8-dioxide.

LEWIS GOT'IS, Primary Examiner. T. MESHBESHER, Assistant Examiner. 

1. A COMPOUND OF THE FORMULA 